The use of the peptides of the formula: EQU R.sup.a -Ser-Thr-Thr-Thr-Asn-Tyr-R.sup.b (I)
where R.sup.a represents an amino terminal residue Ala- or D-Ala and R.sup.b represents a carboxy terminal residue -Thr or -Thr amide or a derivative thereof with an additional Cys- residue at one or both of the amino and carboxy terminals, or a peptide of formula EQU R.sup.1 -R.sup.2 -R.sup.3 -R.sup.4 -R.sup.5 (II)
where
R.sup.1 is an amino terminal residue Thr-, Ser-, Asn-, Glu-, Arg-, Ile- or Leu-, PA1 R.sup.2 is Thr, Ser or Asp, PA1 R.sup.3 is Thr, Ser, Asn, Arg, Gln, Lys or Trp PA1 R.sup.4 is Tyr and PA1 R.sup.5 is preferably a carboxy terminal residue -Thr, -Arg, or -Gly or a derivative thereof with a corresponding D-amino acid as the amino terminal residue, and/or a corresponding amide derivative at the carboxy terminal residue and/or additionally a Cys- residue at one or both of the amino and carboxy terminals
have been disclosed by Pert, et al (U.S. patent application Ser. No. 07/048,148, abandoned). These short peptides inhibit binding of human immunodeficiency virus (HIV) to human cells by blocking receptor sites on the cell surface.
The realization that viruses may exert cell and tissue tropism by attachment at highly specific sites on cell membrane receptors has encouraged investigators to seek agents which would bind at the viral receptor sites of cell membranes, thus preventing binding of a specific virus to these cells. A demonstration of specific receptor-mediated vaccinia virus infectivity being blocked by synthetic peptides has been previously demonstrated (Epstein et al, Nature 318:663-667).
The HIV virus has been shown to bind to a surface molecule known as the CD4 or OKT4 region, which is present on various cells susceptable to HIV infection, including T lymphocytes and macrophages (see Shaw et al, Science 226:1165-1171 for a discussion of tropism of HIV-III).
In addition to symptoms arising from immunodeficiency, patients with AIDS show neuropsychological deficits. The central nervous and immune systems share a large number of specific cell-surface recognition molecules, serving as receptors for neuropeptide-mediated intercellular communication. The neuropeptides and their receptors show profound evolutionary stability, being highly conserved in largely unaltered form in unicellular organisms as well as higher animals. Furthermore, the central nervous and immune systems show common CD4 (OKT4) cell-surface recognition molecules which serve as receptors for the binding of HIV envelope glycoprotein (gp 120). Since the same highly conserved neuropeptide informational substances integrate immune and brain function through receptors remarkably similar to those of HIV, it was postulated a very similar amino acid sequence between the HIV glycoprotein gp 120 and a short peptide previously identified in another context from the envelope region of the Epstein Barr-Virus might indicate the core peptide essential for viral receptor binding. It was postulated that such a peptide would be useful in preventing infection of new cells in patients suffering from AIDS, since it was believed the peptides would bind with receptor cells and block the binding of HIV gp 120, that such peptides binding to the receptor cites would give rise to production of antibodies directed to the peptide sequence, and that these peptides might be used to provide immunological basis for prevention of AIDS.